Search PubMed⌕ Search

Biomedical subjects

D A Clark

Publications and source records attributed to D A Clark.

At least 379 records · Page 21Linked to original sources
PubMed1981

Radioimmunoassay of the leukotrienes of slow reacting substance of anaphylaxis.

A rabbit immunized with a conjugate of leukotriene D4 (LTD4) and bovine albumin via the icosanoid carboxyl produced antibodies with comparable affinities for leukotrienes C4, D4, and E4 (LTC4, LTD4, and LTE4) and their 11-trans stereoisomers. The antibodies bound 3H-labeled 11-trans-LTC4 and 11-trans-LTC4 with the same average association constant (Ka) of 2.8 x 10(9) M-1 at 37 degrees C and were present at a concentration of 0.32 microgram/ml of the immune rabbit plasma. When 9.5 microliter of anti-LTD4 and 108 pmol of 11-trans-[3H]LTC4 (40 Ci/mmol) were incubated in a volume of 300 microliter with LTC4, LTD4, LTE4, or their 11-trans stereoisomers, 50% inhibition of 11-trans-[3H]LTC4 binding was achieved at levels varying between 0.3 and 0.7 ng. As assessed with synthetic analogs of the natural leukotrienes, the antibodies recognized neither those changes within the 6-sulfidopeptide unit of LTD4 produced by deamination or modest peptide lengthening nor the specific stereochemistry of the delta 14-cis double bond. However, the antibodies did recognize the triene lipid domain and the position and spatial orientation of the glutathione or cysteinylglycine function. Binding of 11-trans-[3H]LTC4 by anti-LTD4 was not inhibited by glutathione, cystinylbisglycine, arachidonic acid, or 5-hydroxy-6,8,11,14-icosatetraenoic acid, and leukotriene B4 (LTB4) was about 1/1000th as active as LTC4, LTD4, or LTE4. Mouse lymphoma (WEHI-5) and rat basophil leukemia (RBL-1) cells, when stimulated with calcium ionophore A23187, each produced immunoreactive leukotrienes; and LTC4, LTD4, and LTE4 from RBL-1 cells were individually quantitated by radioimmunoassay after resolution by high-performance liquid chromatography.

Animals↗
PubMed1981

Role of natural killer cells in Pichinde virus infection of Syrian hamsters.

Pichinde virus produced a fatal infection in adult MHA hamsters but not LSH hamsters after intraperitoneal inoculation. After footpad inoculation, an 8-day swelling response was observed in LSH but not MHA hamsters; however, both strains survived infection by this route. Examination of the kinetics of viral replication in the two hamster strains inoculated by the two routes revealed a correlation between infectious centers and natural killer activity in cells obtained from spleens and popliteal lymph nodes. A subpopulation of cytolytic and infected cells which sedimented at about 3.0 to 4.5 mm/h in albumin gradients was found in greater numbers in MHA than in LSH hamsters. These data suggest that one factor contributing to the fatal outcome of Pichinde virus infection in MHA hamsters is the presence of excessive numbers of splenic target cells which possess properties of natural killer cells.

Animals↗
PubMed1981

Early development of infants of birth weight less than 1,000 grams with reference to mechanical ventilation in newborn period.

Growth, development, and neurologic status were assessed at 1 year of age in 38 infants of birth weight less than 1,000 gm who were born in 1976 through 1978. Twenty had received mechanical ventilation as newborns, and this group had a significantly higher incidence of respiratory distress syndrome, seizures, cardiac arrest, bronchopulmonary dysplasia, and retrolental fibroplasia than those not ventilated. The ventilated infants had a high incidence (70%) of bronchopulmonary dysplasia and of retrolental fibroplasia (20% grade III or IV). Seven of eight infants with severe developmental delay (greater than 2 SD), six of nine with moderate delay (greater than 1 SD), and seven of eight with neurologic disability had received ventilation. There was no difference in growth between the ventilated and nonventilated children. Of the total group, 53% showed no problems.

Bronchopulmonary Dysplasia↗
PubMed1981

Perioperative management of patients with paroxysmal nocturnal hemoglobinuria.

During the past two decades, we have had the opportunity to study a large number of patients with the rare hemolytic anemia, paroxysmal nocturnal hemoglobinuria. Sixteen surgical procedures have been performed upon ten patients with paroxysmal nocturnal hemoglobinuria. From this experience, we have developed certain recommendations for preoperative evaluation and preparation, intraoperative management and post-operative care. Any proposed surgical procedure for a patient with paroxysmal nocturnal hemoglobinuria should be closely managed by a team consisting of a surgeon, hematologist and anesthesiologist. In the preoperative evaluation, particular attention should be paid to the hematologic, renal and hepatic status. Transfusion requirements, whether precipitated by hemolytic episodes or surgical blood loss, should be met with either washed or perviously frozen erythrocytes, with consideration of the use of dextran for volume replacement. Dextran is the treatment of choice for thrombotic epidsodes. Close attention should be given to avoiding hypoxia and dehydration. Anesthetic agents which may activate complement or may be hepatotoxic are to be avoided.

Adult↗
PubMed1981

The kidneys in paroxysmal nocturnal hemoglobinuria.

Long-term study of 21 PNH patients revealed an unexpectedly high incidence of functional and anatomic renal abnormalities. Most patients demonstrated varying degrees of hematuria and proteinuria distinct from hemoglobinuria. Evaluation of renal function revealed hyposthenuria, abnormal tubular function, and declining creatinine clearance. Radiologically these patients had enlarged kidneys, cortical infarcts, cortical thinning, and papillary necrosis which were confirmed by autopsy studies. Hypertension developed in eight patients. Urinary tract infection was uncommon. The renal findings bear striking similarity to those of sickle cell anemia. Contrary to the usual opinion, out studies clearly showed evidence of widespread renal pathology in PNH most likely due to repeated microvascular thrombosis similar to the venous thrombosis involving other organs in this disorder.

Adolescent↗
PubMed1980

Physiochemical properties of oviductal fluid from rabbits exposed to heat stress.

Oviductal fluids (OF) were collected at 24 hour intervals from 27 does. Fluids were collected from all does during estrus and subsequent pregnancy or pseudopregnancy. After collecting OF for 15 days from all does maintained at 21 degrees C and 45% relative humidity (RH), approximately one-half of the does were then subjected to heat stress (33.20+/-0.75 degrees C and 65.4+/-2.3% RH). Oviductal fluid was then collected for 5 days from heat stressed estrous does (HSER), after which all does (both control and HSER) were mated to fertile bucks. Human chorionic gonadotropin was administered to each doe to insure ovulation. Fluids were compared between HSER and heat stressed pregnant rabbits (HSPR) and control estrous (NHER) and pregnant rabbits (NHPR) for volume, pH, various protein concentrations, and total protein content. Fluid volume decreased due both to heat stress and pregnancy. Heat stress increased pH, whereas pregnancy resulted in a decrease. Protein concentration of OF from HSER declined due to heat stress. Protein concentration of OF from NHPR increased prior to breeding, peaking at day 3 of pregnancy, then declined to initial levels. While from HSPR there was also a tendency to have a similar increase, the peak in protein concentration was on day 4 and then decreased on day 5. Total protein content (concentration x volume) of OF from HSER decreased due to heat stress. Total protein content from HSPR and NHPR had similar changes with or without heat stress, although the total protein content from OF of HSPR was less (except for day 3) for the entire 5 day period studied. Relative percentages of albumin decreased and postalbumin increased during the first day of pregnancy (NHPR). These trends were reversed (a relative increase in albumin and a decrease in postalbumin) in OF from HSPR.

Journal Article↗
PubMed1980

Slow reacting substances of anaphylaxis: identification of leukotrienes C-1 and D from human and rat sources.

Slow reacting substance(s) of anaphylaxis (SRS-A) was isolated from both human (lung) and rat sources and compared with three synthetic SRS-As of known structure-leukotrienes (LTs) C-1, C-2, and D. Reversed-phase liquid chromatography was used both as a final purification step and a means of comparison of biologically derived and synthetic substances. Two major peaks of SRS-A activity of both rat and human origin corresponded chromatographically with LTC-1 and LTD, respectively, and had equivalent specific activities on the guinea pig ileum. With guinea pig ileum, the specific activities (units/pmol) for synthetic leukotrienes and anaphylactic peaks were (mean +/- SEM): synthetic LTC-1, 1.93 +/- 0.13; SRS-A(rat) peak I, 1.69 +/- 0.43; synthetic LTD, 6.10 +/- 1.15; SRS-A(rat) peak II, 7.14 +/- 0.51; and SRS-A(hu) peak II, 1.90. Both synthetic LTC-1 and LTD and their SRS-A natural counterparts had a preferential contractile activity on guinea pig peripheral airway compared to central airways and were at least 200 times more active than histamine on peripheral airways on a molar basis. Leukotriene D is the major SRS-A of human lung and accounts for almost all of the biological activity. It likely is formed from leukotriene C-1 in vivo by an enzymic process of the well-known gamma-glutamyltransferase type.

Animals↗
PubMed1980

Comparative airway and vascular activities of leukotrienes C-1 and D in vivo and in vitro.

The pharmacologic activities of leukotrienes C-1 and D(LTC-1 and LTD), constituents of slow reacting substance of anaphylaxis (SRS-A), were evaluated in vitro on airway contractile tissues and in vivo on pulmonary mechanical function, mean systemic arterial pressure, and cutaneous microcirculation. In vitro both LTC-1 and LTD were potent and selective peripheral airway agonists, being more active than histamine; furthermore, LTD was active on peripheral airways at concentrations 1/100th those of LTC-1. The concentration-effect relationship for LTD and the profile of antagonism by FPL 55712 are consistent with the activity of this molecule at two separate peripheral airway receptors. In vivo, LTC-1 and LTD were nearly equally active in their effects on pulmonary mechanics, and the pattern of alterations was consistent with the predominant site of action being in the lung periphery. Furthermore, both agents had a direct systemic arterial hypotensive effect and were vasoactive on the cutaneous microcirculation. Thus, these compounds are likely to be major mediators of the pathologic alterations in immediate type hypersensitivity reactions in which peripheral airway constriction and hypotension are prominent features.

Airway Resistance↗